The liver,a critical metabolic organ,is particularly vulnerable to damage upon aluminum exposure.However,the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated.Thi...The liver,a critical metabolic organ,is particularly vulnerable to damage upon aluminum exposure.However,the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated.This study aimed to investigate the adverse effects of aluminum exposure on mouse liver tissue.The results indicated that AlCl_(3) exposure induced significant liver dysfunction,characterized by reduced adenosine triphosphate levels,elevated plasma alanine aminotransferase and aspartate aminotransferase.Histopathological analysis of liver tissue revealed marked histological damage,accompanied by substantial iron deposition.Further examinations demonstrated elevated hepatic levels of malondialdehyde,4-hydroxynonenal,and reactive oxygen species,decreased levels of glutathione(GSH)and superoxide dismutase,increased levels of oxidized glutathione(GSSG),and a reduced GSH/GSSG ratio.The mRNA and protein expression of ferroptosis-related molecules,including downregulated glutathione peroxidase 4 and solute carrier family 7 member 11,were significantly downregulated,while acyl-CoA synthetase long-chain family member 4,ferritin heavy chain 1,and iron regulatory protein 1 levels were significantly upregulated.Treatment with Ferrostatin-1 markedly ameliorated liver dysfunction and histopathological damage,attenuating signs of ferroptosis.These findings highlight the potential of ferroptosis-targeted therapies as a viable treatment strategy for aluminum exposure-induced hepatocyte injury.展开更多
基金supported by the Central Guided Local Development Fund Special Project(No.ZY23055039)the Natural Science Foundation of Guangxi Province(No.2025GXNSFHA069061)+5 种基金Baise City Scientific Research and Technology Development Plan Self-Funded Project(No.Encyclopedia 20241590)Baise City Scientific Research and Technol-ogy Development Plan Project(No.Encyclopedia 20232083)Guangxi Zhuang Autonomous Region Traditional Chinese Medicine Management Bureau Self-Funded Scientific Research Project(No.GZZC2020248)Guangxi Zhuang Autonomous Region Health Commission Self-Funded Scientific Research Project(No.Z20201416)2024 Innovation Project of Youjiang Medical University for Nationalities Graduate Education(No.YXCXJH2024004)the Natural Science Foundation of Guangxi Province(No.GUIKEAB24010060).
文摘The liver,a critical metabolic organ,is particularly vulnerable to damage upon aluminum exposure.However,the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated.This study aimed to investigate the adverse effects of aluminum exposure on mouse liver tissue.The results indicated that AlCl_(3) exposure induced significant liver dysfunction,characterized by reduced adenosine triphosphate levels,elevated plasma alanine aminotransferase and aspartate aminotransferase.Histopathological analysis of liver tissue revealed marked histological damage,accompanied by substantial iron deposition.Further examinations demonstrated elevated hepatic levels of malondialdehyde,4-hydroxynonenal,and reactive oxygen species,decreased levels of glutathione(GSH)and superoxide dismutase,increased levels of oxidized glutathione(GSSG),and a reduced GSH/GSSG ratio.The mRNA and protein expression of ferroptosis-related molecules,including downregulated glutathione peroxidase 4 and solute carrier family 7 member 11,were significantly downregulated,while acyl-CoA synthetase long-chain family member 4,ferritin heavy chain 1,and iron regulatory protein 1 levels were significantly upregulated.Treatment with Ferrostatin-1 markedly ameliorated liver dysfunction and histopathological damage,attenuating signs of ferroptosis.These findings highlight the potential of ferroptosis-targeted therapies as a viable treatment strategy for aluminum exposure-induced hepatocyte injury.
